Targeting in neutrophils enhances the clearance of in infected wounds.

Argonaute 2 bound mature microRNA (Ago2-miRNA) complexes are key regulators of the wound inflammatory response and function in the translational processing of target mRNAs. In this study, we identified four wound inflammation-related Ago2-miRNAs (, , , and ) and show that is critical for infection control. mice exhibited delayed sterile healing with prolonged neutrophil activation and interleukin-6 expression, and markedly improved repair of -infected wounds. We also showed that the expression of was regulated by CCAAT/enhancer binding protein alpha in human neutrophils after exposure to peptides. Treatment with -derived neutrophils, or antisense oligodeoxynucleotides in -infected wild-type wounds markedly improved the healing of these otherwise chronic, slow healing wounds. This study reveals how regulates the bactericidal capacity of neutrophils at wound sites and indicates that targeting might be of therapeutic benefit for infected wounds in the clinic.